Rotaviruses are the single most important etiologic agents of severe diarrheal illness of infants and young children worldwide. Thus, there is an urgent need for a rotavirus vaccine that can prevent severe rotavirus diarrhea during the first two years of life when this illness is most serious. The "Jennerian" approach to vaccination, which involves use of a live vaccine virus strain derived from a non-human host, has been evaluated in clinical trials of (i) a bovine rotavirus by others, or (ii) a rhesus rotavirus (RRV) strain by the Epidemiology Section, LID. This strategy has had limited success because serotype-specific immunity against all 4 epidemiologically important human rotavirus serotypes (specified by outer capsid protein VP7) could not be achieved consistently in infants less than 6 months of age who had not undergone prior rotavirus infection. Highly effective protection was observed when the simian RRV vaccine (VP7 serotype 3) was used to immunize young infants who were later exposed to human rotavirus strains of the same VP7 serotype. However, in other trials in which rotavirus with a VP7 serotype 1 predominated in the community, vaccine efficacy was variable. As a consequence, most recent clinical trials have employed a "modified Jennerian" approach in which a quadrivalent vaccine of broader antigenic coverage (that includes viruses of VP7 serotype 1, 2, 3, and 4) was used for immunization. This vaccine contains RRV (serotype 3) and reassortant rotaviruses containing 10 RRV genes and a single human rotavirus gene that encodes VP7 serotype 1, 2, or 4 specificity. In addition, a naturally attenuated human rotavirus strain, M37, with a VP7 specificity of serotype I and a unique VP4 specificity shared by other neonatal strains belonging to VP7 serotype 1, 2, 3, or 4, is also under evaluation. Phase I trials of the human rotavirus M37 live vaccine have been completed successfully. The M37 rotavirus vaccine was shown to be safe and immunogenic in a clinical study involving 150 young infants (2-4 months of age) and as a consequence phase 2 efficacy trials are now in progress.